Author/Authors :
Carrasco، نويسنده , , Daniel R. and Sukhdeo، نويسنده , , Kumar and Protopopova، نويسنده , , Marina and Sinha، نويسنده , , Raktim and Enos، نويسنده , , Miriam and Carrasco، نويسنده , , Daniel E. and Zheng، نويسنده , , Mei and Mani، نويسنده , , Mala and Henderson، نويسنده , , Joel and Pinkus، نويسنده , , Geraldine S. and Munshi، نويسنده , , Nikhil and Horner، نويسنده , , James and Ivanova، نويسنده , , Elena V. and Protopopov، نويسنده , , Alexei and Anderson، نويسنده , , Kenneth C. and Tonon، نويسنده , , Giovanni and DePinho، نويسنده , , Ronald A.، نويسنده ,
Abstract :
Summary
le myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis.
